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关键词： Adaptive immunity   Cytokines and Chemokines  

关键词： mmp-3   netrin-4   rat model   rotator cuff tears   tnf-α  

摘要： INTRODUCTION:Rotator cuff tears are a major cause of shoulder dysfunction and pain, particularly in older adults, with re-tear rates remaining high despite surgical advances. Persistent inflammation and dysregulated extracellular matrix (ECM) remodeling contribute to impaired healing. Tumor necrosis factor-α (TNF-α) is known to drive tendon inflammation, but the downstream mediators linking TNF-α signaling to matrix degradation remain incompletely understood. Netrin-4 (NTN4), a laminin-related protein, has been implicated in inflammatory and ECM-modulating processes. We hypothesized that NTN4 is upregulated following tendon tear in a TNF-α-dependent manner and contributes to sustained ECM degradation. METHODS:A rat infraspinatus and supraspinatus full-thickness tendon tear model was established, and tendon tissues were harvested at 0 (intact), 7, 14, 28, and 56 days post-injury (n = 8/time point). Gene expressions of , , , , , and were quantified by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Primary rat tenocytes were stimulated in vitro with recombinant TNF-α (0-10 ng/mL) or NTN4 (0-500 ng/mL), and target gene expression and protein secretion were assessed by qRT-PCR and ELISA (enzyme-linked immunosorbent assay). Statistical comparisons were performed using Kruskal-Wallis with Dunn's post-hoc tests. RESULTS:In vivo, expression significantly increased from day 14 onward (P < 0.001), peaking at day 28 and remaining elevated at day 56. and were upregulated earlier (days 7-28), and showed sustained induction (days 7-28), while rose later (day 28). In vitro, TNF-α induced in a dose-dependent manner (P < 0.001). Exogenous NTN4 induced MMP-3 expression at both transcript and protein levels, while no significant changes were observed in MMP-1, TNF-α, or IL-6 protein levels under these experimental conditions. CONCLUSIONS:Our findings identify NTN4 as a TNF-α-induced effector that contributes to sustained MMP-3-mediated matrix d

关键词： tick-borne encephalitis virus   non-structural protein 1   extracellular vesicles   pro-inflammatory cytokines  

摘要： Despite active research, so far the detailed mechanisms of TBEV pathogenesis have not been fully disclosed. Recently, extracellular vesicles, especially small-sized vesicles, which have been shown to play an important role in the pathogenesis of many viruses, have attracted the attention of scientists. In this study, we investigated the effect of the expression of nonstructural protein 1 (NS1) of tick-borne encephalitis virus on the release of extracellular vesicles by cells and assessed the possibility of these vesicles affecting other cells. NS1 expression by TBEV was found to increase the release of extracellular vesicles by HEK293T cells;however, no changes in the size profile of released vesicles were detected. In addition, NS1 is detected in both large and small vesicle size fractions. It was found that NS1 TBEV is not present inside the vesicles, but is associated with their outer surface. Small-sized vesicles derived from the culture medium of NS1-expressing HEK293T cells are able to induce an increase in the mRNA content and interleukin-1 beta (IL-1 beta) secretion in human neuroblastoma SHSY5Y cells. The results indicate the involvement of the NS1 protein and vesicles in the development of neuroinflammation and are important for understanding the mechanisms of pathogenesis of tick-borne encephalitis virus.

关键词： Cytokines and chemokines   Anti-inflammatory agents   Non-steroidal   Innate immunity  

关键词： Observational studies/registry   biological DMARD  

摘要： Background: The 2022 update of the EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs (bDMARDs) addressed several recommendations regarding bDMARDs. Among these, recommendation 10 suggest if a bDMARD or targeted synthetic (ts) DMARD has failed, treatment with another bDMARD or a tsDMARD should be considered. However, there is currently insufficient evidence regarding the efficacy of switching to other target therapies when IL-6 inhibitors are ineffective. Objectives: To evaluate the efficacy of switching from IL-6 inhibitors used as first-line therapy to other targeted molecular therapies in patients with rheumatoid arthritis. Methods: We utilized a database of over 1,600 patients treated with targeted molecular therapies at Osaka Metropolitan University. Patients who initiated Phase 2 therapy with IL-6 inhibitors as their first-line bDMARD and transitioned to Phase 3 therapy were included. Retention rates at 52 weeks and changes in clinical disease activity index (CDAI) were analyzed for each targeted therapy category used in Phase 3. Results: The 52 weeks retention rates after switching from IL-6 inhibitors were as follows: • TNF inhibitors: 91.7% (11/12). • IL-6 inhibitors: 16.7% (1/6) (p<0.01, vs TNF inhibitors). • CTLA4-Ig: 75.0% (3/4) (p=0.383, vs TNF inhibitors). • JAK inhibitors: 37.5% (3/8) (p<0.01, vs TNF inhibitors). Among patients who completed 52 weeks of treatment, the mean CDAI decreased as follows: • TNF inhibitors: 18.7 to 7.7. • IL-6 inhibitors: 22.4 to 22.3. • CTLA4-Ig: 20.0 to 9.9. • JAK inhibitors: 26.5 to 12.2. Retention rates and efficacy were higher with TNF inhibitors and CTLA4-Ig, while IL-6 inhibitors and JAK inhibitors showed lower retention rates and less favorable CDAI improvement. Switching to other IL-6 inhibitors or JAK inhibitors showed lower efficacy and retention rates, potentially due to shared pathways targeting IL-6. This suggests that switching t

关键词： Bone   biological DMARD  

关键词： CD93   interleukin-17D   oxidative stress  

摘要： This review explores interleukin (IL)-17D and its receptor CD93, highlighting their structural, functional, and clinical aspects. Identifying CD93 as the receptor for IL-17D has advanced understanding of the IL-17 family and its signaling pathways. IL-17D, with its unique glycoprotein structure, plays diverse roles in oxidative stress response and potential antitumor therapies. It is involved in autoimmune diseases, infections, and cancers, making it a promising therapeutic target. CD93 is crucial in various biological processes, from angiogenesis to inflammatory diseases. CD93's implications in cancers, neuroinflammation, and metabolism highlight its significance as a potential prognostic marker and therapeutic target. The review emphasizes IL-17D and CD93 as promising areas for future research, offering insights into their signaling pathways and potential applications in personalized medicine. Deciphering the relationship between IL-17D and CD93 is in its infancy and invites exploration for transformative advancements in immunology and beyond.

关键词： Randomised controlled trial   biological DMARD   Clinical Trial   Patient Reported Outcome Measures   Quality of life